Improving Esophageal Adenocarcinoma Prevention, Screening and Treatment Esophageal adenocarcinoma (EAC) incidence has experienced an alarming and largely unexplained 500% increase over the past few decades in the US and much of the western world. Medical and public health efforts to date have primarily focused on endoscopic screening for Barrett's esophagus (BE), a precursor lesion associated with the greatest known risk of EAC development. However, it is not clear if these efforts have impacted EAC mortality as case fatality rates remain high despite substantial utilization of medical resources. The goal of this proposal is to reduce esophageal adenocarcinoma (EAC) morbidity and mortality by using a disease simulation model to systematically evaluate the population-level impact of alternative EAC prevention, screening and treatment strategies. The results will inform clinical guidelines and public health policy that enhances resource allocation including the mitigation of disparities in care by gender, race or ethnicity. The proposed research is innovative as it proposes to change clinical practice where improvements are urgently needed. This grant application is the competing renewal of a previously funded R01 award which focused on the development of a U.S. population simulation model: Esophageal AdenoCarcinoma Model (EACMo). The initial funding has allowed the successful development of EACMo which was used to perform crucial studies that have increased our understanding of EAC and informed clinical care. The proposed research will address the following overarching hypothesis: analyzing specific and pivotal aspects of EAC prevention, screening and treatment using the esophageal adenocarcinoma model (EACMo) will allow the designing of a comprehensive EAC control program that reduces mortality while also optimizing resource utilization. This hypothesis will be investigated by determining the impact of current and future prevention, screening and treatment interventions on EAC incidence and mortality, including the identification of disparities and their impact on survival. This research will determine the effectiveness of alternative strategies within the EAC care continuum. These findings will be incorporated into a comprehensive population model to design an optimized EAC control program that incorporates risk profiles. By the end of the award period, the investigators will have essential evidence to inform clinical and public health guidelines to diminish EAC incidence and mortality while optimizing resource utilization.